Peptic ulcer disease (PUD) is one of the most common diseases affecting GI tract. It causes inflammatory injuries in either the gastric or duodenal mucosa, with extension beyond the submucosa into the muscularis mucosa. The traditional medical approach to treating ulcers is with antacids, H2 receptor blockers and proton pump inhibitors. Cimetidine, famotidine, nizatidine and ranitidine are examples of H2 receptor blockers. Proton pump inhibitors (PPIs) are one of the most commonly prescribed classes of medicines in the primary care setting and are often used in the treatment of acid-peptic diseases. The PPIs reduce the production of acid by inhibiting the enzyme hydrogen-potassium adenosine triphosphatase (H+,K+-ATPase) of the gastric parietal cell that produces acid. The proton pump is the terminal stage in gastric acid secretion and it is responsible for secreting H+ ions into the gastric lumen. The lack of acid in the stomach aids in healing duodenal ulcers. Omeprazole (Prilosec) is a proton pump inhibitor, which blocks the production of acid by the stomach. Several other PPIs such as lansoprazole, rabeprazole, pantoprazole and esomeprazole have been introduced in the clinical practice. However anti-ulcer drugs may increase certain allergies to food. All the PPIs under clinical practice include non-steroidal drugs.
On the other hand, the steroidal aza heterocycles are well known as inhibitors of enzymes such as 5α-reductase and 17α-lyase. Moreover, the steroidal heterocycles such as danazol, deflazacort, cortivazol, nevazol, 2-azasteroid and finasteride, attract much attention due to their biological activities against various ailments like benign prostatic hyperplasia, asthma, 5α-reductase inhibitor, prostate cancer and L-1210 leukemia. However, the biological activity of the steroidal compounds as PPI is not yet known.
Reference may be made to A E Brandstorm US patent 1995, U.S. Pat. No. 5,386,032 wherein, an improved method for the synthesis of 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methyl]sulfinyl-1H-benzimidazole (omeprazole) by reacting 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-1H-benzimidazole with m-chloroperoxy benzoic acid has been reported in a methylene chloride solution at pH 8.0 to 8.6 followed by addition of alkyl formate.
Another reference may be made to C Slemon & B Marcel US patent 1994, U.S. Pat. No. 5,374,730, wherein, omeprazole and lansoprazole are produced from the corresponding acetate-sulfide compounds by a process of oxidation to form the amide sulfinyl compound, followed by alkaline hydrolysis to the sulfinyl carboxylate or salt and decarboxylation.
Still another reference may be made to K Kyogoku, K Hatayama, S Yokomori, J Sawada and I Tanaka US patent 1978 U.S. Pat. No. 4,085,135, wherein preparation of 2′-(carboxymethoxy)-chalcones having anti-gastric and anti-duodenal ulcer activities has been described.
Still another reference may be made to K Amin, M Dahlstrom, P Nordberg & I Starke US Patent 2001, U.S. Pat. No. 6,313,136 wherein, substituted imidazo pyridine derivatives have been reported to inhibit gastric acid secretion and thus can be used in the prevention and treatment of gastrointestinal inflammatory diseases.
Still another reference may be made to N M Gray US patent 2005, U.S. Pat. No. 6,953,808 wherein, optically pure (−)pantoprazole has been employed for the treatment of gastroduodenal ulcers in human while substantially reducing the concomitant liability of adverse effects associated with the racemic mixture of pantoprazole.
Still another reference may be made to V C O Njar, G T Klus & A M H Brodie, Bioorg. Med. Chem. Lett. 1996, 6, 2777 wherein, steroidal 17-imidazolyl- and triazolyl derivatives have been prepared as candidates for 17-lyase inhibitors.
Still another reference may be made to G A Potte, S E Bane, M Jarman & M G Rowlands, J. Med. Chem. 1995, 38, 2403 wherein, steroidal 17-pyridyl derivative (abiraterone) have been reported as active candidate for 17-lyase inhibitors.